In a recent issue of the journal Oncogene, researchers at Cedars-Sinai Medical Center's Maxine Dunitz Neurosurgical Institute describe a molecular mechanism that appears to make malignant brain tumors more vulnerable to chemotherapy after they have been treated with the dendritic cell vaccine.
This finding builds on several studies recently published by the research team. In 2003, they reported that a protein fragment previously found in melanomas also was detected in highly aggressive brain tumors called gliobalstoma multiforme (GBM). The immune system recognizes the peptide, Tyrosinase-Related Protein (TRP-2), as a foreign invader, making it a significant target for immunotherapy.
"Our findings suggest that TRP-2 could be a powerful molecule linking chemotherapy and immunotherapy," said Keith L. Black, M.D., one of the paper's authors, director of the neurosurgical institute and of the medical center's division of neurosurgery and comprehensive brain tumor program.
"Based on our results, it appears that we can improve chemotherapy sensitivity by targeting TRP-2 and possibly other drug-resistant related tumor antigens. This may be a significant step in the fight against brain tumors and other malignant cancers because even as we have been able to develop very powerful and targeted chemicals, tumors have often been able to outmaneuver them," said Black.
In 2004, the researchers documented that the combination of immunotherapy and chemotherapy significantly slowed tumor progression and extended survival of patients suffering from these deadly tumors. The two therapies together were able to accomplish results that neither could achieve by itself. The average length of survival was extended to about 26 months, compared to 18 months for patients who received vaccine alone and 16 months for those undergoing chemotherapy alone.
In a number of laboratory and clinical trials, dendritic cell immunotherapy had succeeded in eliciting a powerful response against brain tumor cells, but significant improvements in length of survival had not been realized. One theory is that the rate at which tumor cells die is too slow to keep pace with the rapid growth and mutation of tumors in the body.
Similarly, chemotherapy directed against GNB has had very little effect. Even new agents specifically designed to attack the DNA of tumor cells and prevent their replication fail. u